Thymoquinone recovers learning function in a rat model of Alzheimer’s diseaseParvinPoorgholamDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, IranauthorParichehrehYaghmaeiDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, IranauthorZahraHajebrahimiAerospace Research Institute, Ministry of Science Research and Technology, Tehran, Iranauthortextarticle2018engObjective: Alzheimer's disease is a neurodegenerative disorder characterized by accumulation of amyloid beta in the hippocampus. In recent decades, herbal medicine has been widely used to treat many neurodegenerative disorders,as in comparison to conventional drugs, herbal remedies exert minimal side effects. Here, the effects of thymoquinone, as the main active component of Nigella sativa, on passive avoidance memory in rat model of Alzheimer’s disease, were evaluated. Materials and Methods: Hippocampal injection of amyloid beta (Aβ) was used to induce Alzheimer’s disease in male Wistar rats, followed by intra peritoneal administrations of 5 and 10 mg/kg thymoquinone on a daily basis for 4 weeks. Animals were subjected to fear learning behavior in passive avoidance test and histopathological analysis of the hippocampus was done. Shuttle box test was used to evaluate the condition studying memory. Thioflavin-S and Hematoxylin and Eosine staining were done to confirm Aβ plaque formation and to evaluate the effect of thymoquinone on the pyramidal cells in the hippocampal CA1 region. Results: Amyloid beta caused cognitive dysfunction reflected by increasing initial and step-through latency along with plaque formation and degeneration of pyramidal cells in the hippocampus. Thymoquinone administration ameliorated this effect by significant reductions in plaque formation in CA1 region of the hippocampus and increased latency time. It also increased the number of surviving neurons in the hippocampus. Conclusion: It seems that thymoquinone improved learning function in a rat model of Alzheimer’s disease. Thus, thymoquinone could be possibly used as an anti-neurodegenerative agent for protecting hippocampal neurons against neurotoxic effects of Aβ in patients with Alzheimer’s disease.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018188197http://ajp.mums.ac.ir/article_10253_78fbcc787aec489d55b71bdffe0673aa.pdfdx.doi.org/10.22038/ajp.2018.21828.1820A systematic review and meta-analysis of clinical trials on saffron (Crocus sativus) effectiveness and safety on erectile dysfunction and semen parametersNahidMaleki-saghooniStudent Research Committee, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, IranauthorKhadijehMirzaiiFaculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, IranauthorHosseinHosseinzadehPharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranauthorRaminSadeghiNuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, IranauthorMorvaridIraniStudent Research Committee, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iranauthortextarticle2018engObjective: We performed this systematic review and meta-analysis study to determine saffron (Crocus sativus) effectiveness and safety in male infertility problems. Materials and Methods: The databases PubMed, Scopus, Cochrane, Google Scholar, SID, IranMedex and Magiran until July 2016 and reference section of relevant articles, were searched to find both English and Persian clinical trials on male infertility issues that used saffron as medical treatment. Also, the quality of these trials was evaluated by Oxford Center for Evidence Based Medicine checklist. A total of six trials was ultimately included. All statistical analyses were done by Comprehensive Meta-analysis (CMA) Version 2. Results: Only in one study conducted on sperm parameters, the mean percentage of sperm with normal morphology (p<0.001) and sperm motility (p<0.001) were increased. Quantitative analysis showed that saffron had a significantly positive effect on all dimensions of Erectile Function questionnaire (MD for Erectile function=5.36(p=0.00), Orgasmic function=1.12 (p=0.007), Overall satisfaction=1.23 (p=0.005), Satisfaction with intercourse=2.18 (p=0.00) and Sexual desire=0.78 (p=0.00), Fixed effects model using 3 trials). The result of subgroup analysis based on dimensions of Erectile Function questionnaire showed statistically significant differences among subgroups (p=0.00). Conclusion: saffron has a positive effect on erectile dysfunction. However, our study showed contradictory results about semen parameters. So, interpretation of results is limited because of methodological flaws of the included studies, erectile dysfunction status and a large heterogeneity among them. Further trials are still needed to confirm the current findings.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

2018210226http://ajp.mums.ac.ir/article_9854_3cb9eb3d26ae1227c1050aa8e33a7c39.pdfdx.doi.org/10.22038/ajp.2017.21164.1800Antinociceptive effect of methanolic extract and alkaloid fractions of Berberis integerrima root in animal modelsValiollahHajhashemiDepartment of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IranauthorForooghFahmidehDepartment of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IranauthorMustafaGhanadianDepartment of Pharmacognosy, Isfahan School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iranauthortextarticle2018engObjective: Berberis vulgaris has antioxidant, hepato--renal protective, antibacterial, lipid lowering, anti-inflammatory and antinociceptive activities. The genus Berberis, has another member called Berberisintegerrima which has not been studied for antinociceptive activity and therefore, this study was aimed to examine the antinociceptive effect oftotal extract and alkaloid fractions of Berberis integerrima root in mice. Materials and Methods: Methanolic total extract and alkaloid fractions of the plant namely, fractions A, B, C and D were prepared according to standard methods. Male Swiss mice (20-25 g) were used (n=6 in each group). Acetic acid-induced writhing, formalin and hot-plate tests were used to assess the antinociceptive activity. In hot plate and formalin tests, morphine (10 mg/kg, i.p.) and in acetic acid test, indomethacin (10 mg/kg, i.p.) were used as reference drugs. Results: The total extract and fractions A, B and D significantly reduced abdominal twitches in acetic acid test and licking behavior of both acute and chronic phases of formalin test. In hot-plate test, morphine as the standard drug demonstrated significant antinociception while the plant extract and fractions were ineffective. The dose of 5 mg/kg of fraction C showed slight analgesia only in acetic acid test and a dose of 10 mg/kg caused severe toxicity and even death in some animals. Conclusion: Berberis integerrima total extract and its alkaloid fractions showed antinociceptive effect and it seems that the mechanism of this action is peripherally mediated since they were effective in formalin test and acetic acid- induced writhing but not in hot-plate test.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018227236http://ajp.mums.ac.ir/article_10002_12bd41390cbde3f840b61f401ffcb89d.pdfdx.doi.org/10.22038/ajp.2017.22827.1850Cuscuta campestris induces apoptosis by increasing reactive oxygen species generation in human leukemic cellsMalihehMoradzadehGolestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, IranauthorAzarHosseiniPharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, IranauthorHasanRakhshandehPharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, IranauthorAzitaAghaeePharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, IranauthorHamidrezaSadeghniaDivision of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iranauthortextarticle2018engObjective: Cuscuta campestris or common dodder is a holoparasitic plant that has been valorized for treatment of liver injury and cancer prevention in traditional medicine. Recently, extract of C. campestris had shown moderate antimicrobial properties and cytotoxic effects. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by hydroalcoholic extract of C. campestris(CCE)(12.5-200 µg/ml), as well as arsenic trioxide (As2O3, 50 µM), in human leukemic (HL60 and NB4) and normal polymorph nuclear cells after 72 hr treatment. Materials and Methods: Resazurin assay was used to determine cell viability following treatment with C. campestris. Intracellular reactive oxygen species (ROS) and apoptotic cells were measured by fluorimetry using carboxy 2′, 7′-dichlorofluorescein diacetate and propidium iodide (PI), as staining reagents, respectively. The differentiation of leukemic cells was evaluated by Giemsa staining and nitro blue tetrazolium (NBT) reduction. Results: C. campestris inhibited cell viability with IC50 values of 23.9 µg/ml for HL60 and 60.3 µg/ml for NB4 cells after 72 hr treatment. ROS formation was also concentration-dependently increased following treatment with C. campestris. In addition, the number of apoptotic cells significantly increased to 88.4% and 62.3% in CCE (200 µg/ml)-treated HL60 and NB4 cells, respectively, which was higher than that of As2O3 (50 µM)-treated leukemic cells (p<0.001). Nonetheless, C. campestris did not induce differentiation of leukemic cells towards granulocytic pattern. Conclusion: The present study demonstrated that C. campestris induced apoptosis through ROS production without having differential effect on leukemic cells, in concentration- and time-dependent manners. Understanding of precise signaling pathway by which C. campestris induce apoptosis, needs further researchAvicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018237245http://ajp.mums.ac.ir/article_10011_f01e938772267964ca1670385269cf35.pdfdx.doi.org/10.22038/ajp.2017.22557.1866In vitro evaluation of antibacterial activity of verbascoside, lemon verbena extract and caffeine in combination with gentamicin against drug-resistant Staphylococcus aureus and Escherichia coli clinical isolatesBibi SedighehFazly BazzazBiotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, &lrm;Mashhad, IranauthorbahmankhamenehDepartment of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, &amp;lrm;&amp;lrm;Mashhad, IranauthorMohammad RezaZahedianScStudents Research Committee, School of Pharmacy, Mashhad University of Medical SciencesauthorHosseinHosseinzadehPharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of &lrm;Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iranauthortextarticle2018engObjective: In recent years, there has been an increasing interest in using herbal products to overcome bacterial resistance. The aim of this study was to investigate the effect of lemon verbena aqueous extract, verbascoside and caffeine in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus and Escherichia coli strains. Materials and Methods: The MIC and MBC values of different antibacterial agents against bacterial strains were determined. The effect of co-administration lemon verbena extract, verbascoside, and caffeine and gentamicin was studied in vitro using a checkerboard method and calculating fraction inhibitory concentration index (FICI). Results: Herbal extract, verbascoside and caffeine alone showed no inhibitory effects on any of the bacterial strains (at doses up to 200 mg/ml). Herbal extract, verbascoside and caffeine were able to decrease the MIC of gentamicin against the standard resistant strains and two clinical isolates. Among these combinations, the co-administration of verbascoside and gentamicin was more effective and synergistic activities (FICI<1)‏ against clinical isolates were observed.‏ Conclusion: The results of the present study revealed that herbal extract, verbascoside and caffeine potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and E. coli.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018246253http://ajp.mums.ac.ir/article_10211_58b96259b834416816a71dc69fc5392e.pdfdx.doi.org/10.22038/ajp.2018.15338.1607Protective effect of Urtica dioica leaf hydro alcoholic extract against experimentally-induced atherosclerosis in ratsFatemehNamaziDepartment of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, IranauthorTahooraShomaliDivision of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranauthorPouyaTaghikhaniDivision of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine,
Shiraz University, Shiraz, IranauthorSaeidNazifiDepartment of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shirazauthortextarticle2018engObjective: Finding compounds that could be used for prevention of atherosclerosis (AS) is highly desired. The present study evaluated the protective effects of Urtica dioica (UD, commonly known as stinging nettle) leaf ethanolic extract against high-fat diet-induced AS in rats. Materials and Methods: In this study, 40 male adult Sprauge-Dawley rats were randomly allocated to 4 equal groups and treated as follows for 9 consecutive weeks: (1) Normal control (NC; normal rats that were fed with a basic diet); (2) Atherosclerotic rats (AT; which received no particular treatment); (3) Atherosclerotic rats that received 100 mg/kg/day ethanolic extract of UD orally and (4) Atherosclerotic rats that received simvastatin 4 mg/kg/day orally. Atherosclerosis was induced by a high-fat diet accompanied by propylthiouracil and vitamin D3. Results: Marked hypercholesterolemia and significant increase in LDL-C/HDL-C ratio were observed in rats of AT group. Administration of UD significantly reduced these parameters as compared to AT group (p Conclusion: Ethanolic extract of UD prevents establishment of atherosclerotic lesions in rat aorta, which is associated with positive effects on serum lipid profile without significantly affecting antioxidant status.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018254262http://ajp.mums.ac.ir/article_10264_c213ff071a904bbe63f00b1602ef2c61.pdfdx.doi.org/10.22038/ajp.2018.25213.1917Early and late preventive effect of Nigella sativa on the bleomycin-induced pulmonary fibrosis in rats: An experimental studyHamid RezaPoursalehiPhysiology Research Center of Kerman University of Medical Sciences, Kerman, IranauthorMitraSamareh FekriCardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IranauthorFaribaSharififarDepartment of Pharmacognosy, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, IranauthorAliMandegaryDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Science, Kerman, IranauthorAtefehIzadiDepartment of Pharmacy, Kerman University of Medical Science, Kerman, IranauthorRahilMahmoodiDepartment of Pharmacy, Kerman University of Medical Science, Kerman, IranauthorMohammad HadiNematollahiHerbal & Traditional Medicines Research Center, Faculty of Pharmacy Kerman University of Medical Sciences, Kerman, IranauthorFatemePorgholamhoseinDepartment of Pharmacy, Kerman University of Medical Science, Kerman, IranauthorVahidehGhoraniNeurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranauthorMasomeSamareh FekriAssistant Professor of Plant Protection, Departement of agricultureauthortextarticle2018engObjective: Pulmonary fibhrosis is a disease of the connective tissues in the respiratory system. Nigella sativa has been used for the treatment of pulmonary diseases like asthma. This study investigated the early and late preventive effect of methanolic extract of N. sativa on a bleomycin- induced pulmonary fibrosis model. Materials and Methods: This study was carried out using 52 rats. Pulmonary fibrosis was induced by a single endotracheal injection of bleomycin (5 mg/kg). Extract of N. sativa (500 mg/kg per day) or methylprednisolone succinate (4 mg/kg per day) was injected intraperitoneally in two periods (i.e. days 1-14 as early preventive group and days 15-28 days as late preventive group). The lung tissues were histologically examined at the end of each period and inspected for the amount of hydroxyproline and biomarkers of oxidative stress. Results: The pulmonary inflammation and fibrosis were significantly decreased in groups treated with methylprednisolone and N. sativa extract compared to bleomycin group in both early and late prevention groups (p<0.001). The hydroxyproline concentration in pulmonary tissue was significantly decreased in N. sativa and methylprednisolone groups compared to the bleomycin group in both prevention groups (p<0.001). Significant reductions in lipid peroxidation (p<0.001) and increases in catalase activity were also observed in N. sativa and methylprednisolone groups compared to bleomycin group. Conclusion: This study suggested that N. Sativa extract is effective for early and late prevention of pulmonary fibrosis and inflammation. However, more studies are needed to identify its anti-inflammatory and anti-fibrotic mechanisms in the respiratory system.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308

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2018263275http://ajp.mums.ac.ir/article_10265_d1cfa786d65199120d2d71a04b991527.pdfdx.doi.org/10.22038/ajp.2018.26259.1951A comparison between the effects of Portulaca oleracea seeds extract and valsartan on echocardiographic and hemodynamic parameters in rats with levothyroxine-induced thyrotoxicosisRoghayehPakdelDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranauthorSaeedNiazmandDepartment of Physiology and Cardiovascular Research Center, School of Medicine Mashhad University of Medical Sciences Mashhad, IranauthorMohsenMouhebatiCardiology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, IranauthorMohammad MahdiVahediDepartment of pharmacology, faculty of medicine, Mashhad university of medical sciences,Mashhad,IranauthorAzitaAghaeePharmacological Research Center of Medicinal Plants, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical SciencesauthorMousa-al-rezaHajzadehDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iranauthortextarticle2018engObjective: The aim of the present study was to compare the effects of Portulaca oleracea (Po) seeds extract and those of valsartan on cardiac function in levothyroxine (T4)-treated rats. Materials and Methods: Forty Wistar rats were divided into four groups (n=10): control, levothyroxine (T4), T4 plus valsartan (T4-Val) and T4 plus hydro-alcoholic extract of the P. oleracea seeds (T4-Po). Control group received normal saline. Levothyroxine (100µg/kg/day, i.p.) was administered to three other groups for 4 weeks. Valsartan (8 mg/kg/day, orally) and Po seeds extract (400 mg/kg/day, orally) were administered during the last two weeks of treatment period. At the end of the experiment, echocardiographic and hemodynamic parameters were measured and serum free T4, T3, and T4 were measured. Results: Administration of T4 for 4 weeks significantly increased serum free T4 levels in T4 group but elevations of free T4 levels in T4–Val group were not significant. Free T4 level decreased in T4–Po (p<0.01) compared to T4 group. Heart rate (HR), heart weight (HW), and left ventricular systolic pressure (LVSP) were significantly increased in T4 group compared to control group while these parameters in the other groups were not significantly different from those of control group. The reduction in HR, HW, and LVSP were more prominent in T4-Po group. Ejection fraction (EF) and fraction shortening (FS) were insignificantly decreased in T4 group compared to control group. Conclusion: These results showed that treatment of hyperthyroid rats with P. oleracea seeds extract was more effective than valsartan in reducing cardiac changes induced by levothyroxine.Avicenna Journal of PhytomedicineMashhad University of Medical Sciences2228-79308